Lecture 20: Fatty Acid Synthesis Flashcards

1
Q

acetyl CoA carboxylase

A

key regulated enzyme in fatty acid synth

generates malonyl CoA using acetyl CoA

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2
Q

malonyl CoA

A

where the growing fatty acids attach

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3
Q

whats the reductant in fatty acid synth

A

NADPH

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4
Q

what moces the acetyl coA equivalents from the mitochondria to the cytosol

A

citrate shuttle

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5
Q

review table in slide

A

3

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6
Q

what is the common metabolite in both the synthesis and degradation pathways

A

acetyl CoA

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7
Q

why does it make sense that fatty acid degredation takes place in the mitochondrial matrix

A

NADH and FADH2 are produced

they’re ready to enter the ETS if they’re present

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8
Q

what purpose does fatty acid synth serve

A

convert excess acetyl CoA to fatty acids to be stored or exported (when glucose levels are high)

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9
Q

key enzymes in FA synth?

A

acetyl coA carboxylase

fatty acid synthase

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10
Q

is the energy charge high or low in the cell when excess acetyl-CoA is available for fatty acid synthesis?

A

high!

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11
Q

swinging arm mechanism

A

2 domain protein and biotin carrier

covalent linkages so intermediate doesn’t diffuse away

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12
Q

How many NADPH must be oxidized in the synthesis of C16 fatty acid palmitate shown on slide 11?

A

14

we need two every time we add 2 carbons
7 x 2= 14 NAPDHs

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13
Q

How many CO2 are released in this process and where are they coming from?

A

7 are released because we go through the process 7 times

they come from the malonyl CoA

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14
Q

review slides 10 and 11

A

review slides 10 and 11

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15
Q

there are 7 dehydration steps required for palmitiate synthesis
why only 6 NET H2O???

A

at the end of the cycle, we still have an acyl chain bound, but it takes water to release it

we produce 7 water molecules but we use one to release the chain

needed for final cleavage rxn to release palmitate from the ACP carrier protein

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16
Q

where do we add the carbon?

A

not at the end, but closer to the begining

17
Q

write the reaction for synth of C18 stearate

__acetyl CoA + __ATP + __NADPH +__H+ —> sterate+__CoA+__ADP+__Pi+__NADP+ + __H2O

A

9 acetyl CoA +8 ATP + 16 NADPH +16 H+ —> sterate+9 CoA+8 ADP+ 8 Pi+ 16 NADP+ + 7 H2O

18
Q

How do we move acetyl CoA

What do we do with it

A

we don’t directly transport it
use shuttle system

make it citrate that we move to cytosol

19
Q

what do we do with the citrate we put it the cytosol

A

make OAA or carbon and acetyl CoA

make it to malate

20
Q

2 things that can happen to malate

A
  1. transport back to matrix, covert to OAA

2. convert to pyruvate and also produce NADPH (one for every acetyl CoA equivalent)

21
Q

where does most NADPH come from for fatty acid synth??

A

pentose phoshphate pathway (oxidative phase)

so lots of glucose 6 phosphate, make lots of NADPH

22
Q

the bulk of NADPH needed for fatty acid synth actually comes from pentose phosphate pathway. Why does this make sense in terms of glucose 6 P lelvels

A

G6P levels are high during FA synth

we can do this and produce lots of NADPH

23
Q

Metabolic reg of acetyl CoA carboxylase:
what stimulates
what inactivates

A

citrate activity stimulates
palmitoyl coA inhibits

BOTH ALLOSTERIC

24
Q

why does it make sense that excess citrate activates acetyl CoA carboxylase activity?

A

high energy charge, so we need to start storing extra nrg just as fast

25
Why should palmotyl CoA inhibit enzyme activity?
palmitoyl CoA is in fatty acid degredation. Inhibits enzymes in order to inhibit simultaneous synth and degredation
26
Hormonal regulation of Acetyl-CoA carboxylase
glucagon isnulin citrate
27
explain the logic of insulin and AMP reg of acetyl CoA carboxylase
blood sugar levels high, stim by AMP b.c. low nrg charge
28
Why would high citrate levels partially activate the phosphorylated enzyme?
citrate=high nrg charge allosteric reg=fast response (hormones are slow) (review slide 18)
29
Glucagon signaling
cascade of rxns inside cell AMPK (kinase) activated at the end--phosphorylates acetyl CoA carboxylase monomeric state INACTIVATE
30
Citrate
polymerization PARTIAL ACTIVITY phosphorylated, so inactive, but citrate makes it partially active
31
Insulin signaling
protein phosphtase 2 stim: takes off phosphate active state ACTIVATE
32
AMPK
regulated by AMPKK (this one phosphorylates AMPK) AMPKK inactivated by insulin ensures acetyl-CoA carboxylase will stay in active conformation review slide 19
33
review slide 20
review slide 20